Dew, Interesting findings implying a thrombolytic effect of combination therapy. So to speculate: HD ATIII role is in prevention, that is it provides a missing (or at least decreased level of) a factor that prevents thrombin induced conversion of fibrinogen to fibrin thus reducing the likelyhood of clot formation. In the ovine pulmonary burn model presumably clot from release of tissue factors etc is preexistant in the pulmonary tree and then the combination of heparin plus ATIII is administered, implying thrombolysis (and ? antiinflamatory effects). Wonder if we could analogize to heparin resistance in long pump runs in CABG patients where the heparin requires the presence of ATIII to have any anticoagulation effect at all. Am far removed from the world of hematology except for clinical use of heparin in standard situations so I offer this up as speculative based on no "bench" knowlege. Regards, bp

Louis, I agree and have always been interesting in the "sleeping" ELN connection. thought ressurection of tysabri would be wonderful and now wonder if Biogen had been sold it would have somehow released eln to persue other manufacturing modes?? I don't think you are reaching in noting the possible connection. regards, bp

Dew, with you at .89 Regards, bp I think current drop is a previously unreported side effect of Rucin. Go Huskers.

Louis, Thanks for saving me the time in tracking this down. Go Huskers! bp

Dew, Will retrace my internet search steps as soon as I have a minute and see where I ran into this. Might have been in a grant support application but it was there-- could have knocked me over with a feather. bp

Dew and fellow board members, Have had an interesting time following the Progenetics thread. It has led me to Indus (I may not have spelled this correctly), an Indian Company with JV with Progenics, Novo Nordisk, the US ARMY (fibrinogen bandage) and amazingly, oral therapy for hemophelia (I was previously limiting my thinking to a transgenic plasma factor substitute that would be of necessity have to be given IV). Again as with Pharmathene, the military role for trangenically derived medicines is apparent. I am reassured that finding a partner for GTCBs ongoing activities will not be hard and many suitors are probably lined up. Dew, you have probably summed all this up in the read me first section but it really is worth emphasizing that the technology is sound and valuable, patience worthwhile. bp

Dew, Really now, as the most respected poster on this board you can certainly see why cro and others are concerned. No combat is require here but rather support of each other (if you feel justified) or else cogent advice as to why we too should be selling. Since I don't see any new problems here other than the fact that soon we (GTCB) will have less and then no money in the bank in the face of great progress and good news and a bright future, perhaps it is a case of "if you can keep your head, while others are losing theirs" (with apologies to RK), than that's what we should be helping each other do. Regards, bp

Dew, I have read that quote before but even with FDA approval pending or done, with no sales in the US by that time (surely the usual time delays between approval and sale apply) I don't see cash in the coffers. As my Grandfather used to say "No money?, No money." Let me know if you think this "gap" would be closed by the partner to allow ongoing operations until US sales ramp up. Also I am sure in the read me first list that you kindly keep up for us is an answer to this next question and maybe you can just direct me there, what is the anticipated market for Atryn in the US HD indication? Thanks, Hope you and all the other board members had a great Thanksgiving. "Gratitute can only be given, but never taken." bp

Dew, Even with current infusion (speculated to be 6 to 8 million) for Q 4 from as yet unknown American partner, with current cash to last to Mid 2008 and little to come from European Atryn sales for HD, can you get at some estimate (unless there is a surprise) and sense of the risk of just running out of money? Dr. Cox says he does not plan to return to the markets for cash. Clearly some pharma (or DoD?) will have to ride to the rescue. There is so much great stuff going on at GTCB but not too much income generation. I would like to pick up some more shares at this price but we seem pretty close to the cliff of empty coffers. How about a little optomistic reassurance from the professor. Thanks, bp

Dew, Decimation at MNTA (As Motley Fool, or someone anyway, says "Momentum Stopped"). I think one important lesson is the value FDA puts on immunogenic data which of course GTCB will have completely submitted 90 days after last patient data collected. MNTA may be required to run another trial! Their timeline appears to be changed considerably even though they may have a good drug in M -enoxyperin. Once a large supply of AT III available one wonders what opportunities exist for evaluation as an improved subsitute for existing IV anticoagulants will be e.g. in acute MI (TIMI 10 to the 6th) or acute PE. We were kindly provided priliminary data on this board re promise of activity in acute thrombotic stroke in an animal model. This is a great board by the way. I quess you know that. I am also following GERN closely and it gives me great hope as to what thay may accomplish also. Regards, bp

I remember now, thanks for the reminder. Too bad too since it looked pretty promising and was a reason I increased my holdings then....bp

I note the Fresenius albumin program is still listed. Is this old info or is this something just not mentioned because of stagnation. bp

It does seem odd that all the efforts of our goats seem to have been directed to developemnt of medicines for humans and not animals where the market must be large and less regulated. This is the first I have seen articles such as this but assume since the protein is made in the milk of an animal that gtcb owns the IP. Anyone know of any other examples? pb

Thanks. bp

When one says "top line" data, as mentioned by Dr. Cox regarding the Atryn phase III US data, what does that mean? As opposed to "bottom line" data. Does it mean it has not been fully analysed?? bp

Keep in mind that many of these patients will die of other comorbities, disseminated infection, malignancy, toximia, intracranial bleeding, acute renal failure and so on. Treating the DIC will help take that major contributer to mortality down but large numbers of very sick patients will need to be looked at to see the survival improvement we hope for by treating one of only several causes for demise. In the meantime if some as yet undefined advantage for the ART product emerges we in the deep(er) stuff. Flo, any idea when the Phase II data from Merrimack might be available? bp

My error. Could in theory a phase IIb study (if extremly positive) serve as a basis for approval or is a phase III study always necessary. If for example a survival benefit were shown in spite of the original design that was not powered to do so. Thanks, bp

Floblu14, First of all thank you for helping me get my email problem fixed. The copy and paste solution was a major "duh" on my part but the pop up problem was real and no other solutions suggested by other board members worked. You think the ART-1 investors are not happy because of study outcome? If the company were not happy I doubt we would be seeing an 800 patient phase III study and the financial resources that entails. So, in reading the paper posted by Dew, there was inbetween the lines oblique reference to antithrombin as another anticoagulant in a 1999 paper that compared six anticoagulants. If I have time I will try to get this and review for the board. Also Dr. Cox has always mentioned ATIII has antiinflamatory effects also and anyone knowlegeble who can contrast this to the protein C mediated antiinflammatory effects of the ART product might give us a window into similarities and differences. T 1/2 of thrombomodulin seems longish this could be good or bad, does anyone know how this compares to ATIII (always good to just shut off a drip and have a short T 1/2 if for so reason one needs to. I agree the Art results don't seem that impressive. Those who have treated DIC with heparin know it is worthless. Is the control arm in the phase III ART study heparin or nothing. (Would that there were a third arm of AT III!) Especially with such a large study powered for survival. The ART study looked like it took about 5 years! And multiple sites were part of it. Wonder if our strategy is to have smaller and faster phase III study that could be stopped by data safety and monitoring board if results were great. Regards, to all Let me know if anyone is interested and I can persue trying to get selected papers from the bibliography for the board unless Dew or Flo already have them in their files. Regards to all, bp

ThomasS, Hard to actually elaborate on an idea based on no hard data but here are my thoughts. When collaborations are listed that accompany GTC announcements, Elan seems to be always causually mentioned. Most other erstwhile big pharma relationships are no longer on the list although at one point there were several. I believe GTC made tysabri for ELAN at one point and then the project was shelved but implications from previous company announcements were that it could be revived either because of saved sperm or founder goats (my speculation only) otherwise why would there be continued suble name dropping? Tysabri as a monoclonal is now approved for MS and Crohn's (I think approval has been finalized for the latter), in any case I can't help but wonder how attractive it might be for Elan to have endless supplies of tysabri available at a fraction of the current manufacturing costs, especially now that there is approval in Europe. The above is just based on recollections of announcements that are probably years old and may not be accurate, nonetheless I still see Elan and GTC in the same paragraph at times and wonder why the continued relationship. That's the best I can do--these thoughts are based on nothing substantial. Kind of like Seinfeld's show about nothing, but it sure had me in stitches (and they made a lot of money.) bp

Dew, Production costs notwithstanding. If ART-123 were ever proven superior to Atryn in our medical enviornment patients or even the "system" would pay the difference. I am still interested in trying to understand the role of protein C and if the anti inflamatory effects of each agent would be equivalent. By the way I continue to look for the unexpected curve ball in that Elan continues to be mentioned as a big pharma partner and the tysabri program while previously put in suspended animation, seems ripe for rebirth. regards, bp

Dew, If I read the previous studies re Atryn it looks like there is no effect on circulating protein C but there is with thrombomodulin. Can you help me understand how that difference might play out? It gives me severe agita to see this size study preceding the Atryn phase II study and that means they would almost certainly get to market first assuming positive results, unless off label use for atryn presumably on the market in the US sooner because of HD indication. What are your thoughts??? Regards, bp

Can anyone help me understand why this study is posted on a US gov site when it is only involving European Centers? Are they getting ready to enroll patients in the US too? Perhaps after Phase III HD study? Thanks

Flo, Please don't tell me now that Dew has multiple personalities and you are one of them! This is an interesting patent application. Do you or any of our fellow boarders follow GERN? The manufacture of GERN 163L for the inhibition of telomerase looks interesting. This agent has been hinted to be a potential "cure" for cancer particularly because of its effect on cancer stem cells. Interesting in vitro studies (especially in MM), with embryonic (so to speak) experience in the clinic. This is why I asked Dew earlier about the internal monoclonal antibody program wondering if there was potential to manufacture this anticancer agent. Thus far little clinical evidence (three patients in CLL receiving drug in therapeutic range with two apparantely having a response.) The stock tanked recently because the results were not (yet) indicative of a paradym shift. Could our goats make this? GTC does have a relationship with GERN via START licensing for nuclear transfer technology for other program(s). Regards Maj. General Flo from Private first class bp

Dew, Thank you for continuing to show leadership by insisting on a standard of civility and focus for this board. It continues to be a breath of fresh air with useful and stimulating discussions that have helped me understand this technology and potential far beyond what I might have accomplished alone. Just a brief look at what we once had at Yahoo before you led us through the red sea (unfortunately its still red), to this type of quality discussion board should reinforce exactly what you are doing. The work and research you do on our behalf is duly noted and deeply appreciated. (And thanks also to Lt. first class floblu) Regards, bp

What's the first? Telomerase? Thanks bp

Flo and Dew, the EULR abstracts have been posted on their site. A cursory look did not turn anything up re MM093 but there were a lot of abstracts and I didn't have tome to examine carefully. bp

Thank you Dew as always. I think the future here looks great.

Dew, Can you speculate as to why MM 093 might be more advantageous to RA patients than say Tysabri monotherapy--eg no PML. Also posted preveiously is finding of "statistical significance" of MM 093 in RA patients of < 2 years duration. This to me seems a pretty big deal but no analysis on this (the only worthwhile) board. Also, have not yet listened to conf call, any mention of European enrollment in DIC study? regards, bp

Flo, Dew and mb, I did see on gov trials site that there was a "trend toward significance" in chronic RA patients BUT in patients with RA of less than 2 years duration that results with MM 093 were statistically significant. Did anyone else see this and what is your take? I would think this finding would engender some serious discussion and will probably be the focus of the paper at the EULR. Higher dose study proceding as noted. There was an unclear statement regarding adverse effects from the "drug" occuring in the placebo group. This is not clear of course. Can anyone clarify? It was interesting to note little board discussion re the Merrimack announcement of April 17th. I was out of the country and am now reviewing older posts with interest. Flo of course right on with info re EULR presentation and press release--thank you! Any speculation as to whether PML might be a potential adverse effect (a la Tysabri)especially in patients already on an immunosuppressant such as MTX. Regards to all, Should be an interesting summer with the release of Atryn and presentation of positive MM093 results. bp

Flo, "trial data quite impressive..." This is based on what? It seems that higher doses are being tested but we know little to nothing about results with lower doses as of now. Can you enlighten? Also no recognition of goat role noted in press release. Do you think they want to play this down re patient acceptance. If I had RA and my effective treatment was made in goats and pure, I would probably feel better about it than a plasma derived product (obviously not possible here). I don't think mode of production will affect patient acceptance if it works and might actually be reassuring re purity of product. regards, bp

There's hope! Thanks.

Flo, mea culpa...was feeling sick (fluish)about goats recent performance so this must explain my lapse. But my question stands in that if they are truly presenting at European arthritis conference an abstract title should be available by now. If it is not perhaps we will see yet more information delay. bp

Flu, Would expect at least a title for presentation at purported presentation of MM 093 results from Merrimack at the European arthritis conference by now. Does such a title or agenda of presentations exist (yet)? Thanks bp

Dew, Any idea what "off label" restrictions exist in Europe? Once market release for Atryn in June can you speculate as to whether indications such as outlined here might go forward without formal approval for this specific indication? Others might include heparin resistance for CABG (already data here but not approved for this indication)etc. One might also wonder if compassionate use or "off label" use might be considered by some physicians in other aquired AT 111 deficient states such as DIC even though (presumably) formal studies are going forward simultaneously. Thanks, bp

I must say, if memory serves, this is exactly what you predicted perhaps a year ago. Don't let it go to your head. Regards, bp

Dew, Any speculation as to the applicability of current or future programs of this technology? Is ACT still a player here? I know they lost some patent fights with GERN. Thanks bp

Dew, What ever happened to Merrimacks work on Myasthenia Gravis?

Floblu Again thanks for keeping us informed. bp

Dew, In last conference call Dr. Cox alluded to slow enrollment in US study, do remember this? I suspect we will see delays in the timeline outlined...bp

Thank you Dew as always for keeping us up todate. Await the RA and psoriasis data with interest. Doubt they would be persuing other areas like uveitis without substantial data from their previous studies. June European arthrits meeting awaits...bp